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Zinc-Doped Copper Oxide Nanocomposites Inhibit the Growth of Pancreatic Cancer by Inducing Autophagy Through AMPK/mTOR Pathway

Zinc doped copper oxide nanocomposites (Zn-CuO NPs) is a novel doped metal nanomaterial synthesized by our group using the sonochemical method. Our previous studies have shown that Zn-CuO NPs could inhibit cancer cell proliferation by inducing apoptosis via ROS-mediated pathway. In the present study...

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Autores principales: Li, Xiao, Xu, Huanli, Li, Cong, Qiao, Gan, Farooqi, Ammad Ahmad, Gedanken, Aharon, Liu, Xiaohui, Lin, Xiukun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454023/
https://www.ncbi.nlm.nih.gov/pubmed/31001120
http://dx.doi.org/10.3389/fphar.2019.00319
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author Li, Xiao
Xu, Huanli
Li, Cong
Qiao, Gan
Farooqi, Ammad Ahmad
Gedanken, Aharon
Liu, Xiaohui
Lin, Xiukun
author_facet Li, Xiao
Xu, Huanli
Li, Cong
Qiao, Gan
Farooqi, Ammad Ahmad
Gedanken, Aharon
Liu, Xiaohui
Lin, Xiukun
author_sort Li, Xiao
collection PubMed
description Zinc doped copper oxide nanocomposites (Zn-CuO NPs) is a novel doped metal nanomaterial synthesized by our group using the sonochemical method. Our previous studies have shown that Zn-CuO NPs could inhibit cancer cell proliferation by inducing apoptosis via ROS-mediated pathway. In the present study, we studied the anticancer effect of Zn-CuO NPs on human pancreatic cancer cells. MTS assay revealed that Zn-CuO NPs was able to inhibit cancer cell growth. TEM, flow cytometry and fluorescence microscope analysis showed that Zn-CuO NPs induced autophagy significantly; the number of autophagosomes increased obviously in cells treated with Zn-CuO NPs. Western blot analysis revealed that treatment with the NPs resulted in activation of AMPK/mTOR pathway in both AsPC-1 and MIA Paca-2 cells in dose dependent manners. Moreover, in the presence of AMPK activator AMPKinone, the protein level of p-AMPK, p-ULK1, Beclin-1 and LC3-II/LC3-I increased, while the protein expression of p-AMPK, p-ULK1, Beclin-1 and LC3-II/LC3-I decreased in the presence of AMPK inhibitor Compound C. In vivo study using xenograft mice revealed that Zn-CuO NPs significantly inhibited tumor growth with low toxicity. Our study confirms that Zn-CuO NPs inhibit the tumor growth both in vitro and in vivo for pancreatic cancer. AMPK/mTOR pathway plays an important role in the NPs induced inhibition of tumor growth.
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spelling pubmed-64540232019-04-18 Zinc-Doped Copper Oxide Nanocomposites Inhibit the Growth of Pancreatic Cancer by Inducing Autophagy Through AMPK/mTOR Pathway Li, Xiao Xu, Huanli Li, Cong Qiao, Gan Farooqi, Ammad Ahmad Gedanken, Aharon Liu, Xiaohui Lin, Xiukun Front Pharmacol Pharmacology Zinc doped copper oxide nanocomposites (Zn-CuO NPs) is a novel doped metal nanomaterial synthesized by our group using the sonochemical method. Our previous studies have shown that Zn-CuO NPs could inhibit cancer cell proliferation by inducing apoptosis via ROS-mediated pathway. In the present study, we studied the anticancer effect of Zn-CuO NPs on human pancreatic cancer cells. MTS assay revealed that Zn-CuO NPs was able to inhibit cancer cell growth. TEM, flow cytometry and fluorescence microscope analysis showed that Zn-CuO NPs induced autophagy significantly; the number of autophagosomes increased obviously in cells treated with Zn-CuO NPs. Western blot analysis revealed that treatment with the NPs resulted in activation of AMPK/mTOR pathway in both AsPC-1 and MIA Paca-2 cells in dose dependent manners. Moreover, in the presence of AMPK activator AMPKinone, the protein level of p-AMPK, p-ULK1, Beclin-1 and LC3-II/LC3-I increased, while the protein expression of p-AMPK, p-ULK1, Beclin-1 and LC3-II/LC3-I decreased in the presence of AMPK inhibitor Compound C. In vivo study using xenograft mice revealed that Zn-CuO NPs significantly inhibited tumor growth with low toxicity. Our study confirms that Zn-CuO NPs inhibit the tumor growth both in vitro and in vivo for pancreatic cancer. AMPK/mTOR pathway plays an important role in the NPs induced inhibition of tumor growth. Frontiers Media S.A. 2019-04-02 /pmc/articles/PMC6454023/ /pubmed/31001120 http://dx.doi.org/10.3389/fphar.2019.00319 Text en Copyright © 2019 Li, Xu, Li, Qiao, Farooqi, Gedanken, Liu and Lin. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Li, Xiao
Xu, Huanli
Li, Cong
Qiao, Gan
Farooqi, Ammad Ahmad
Gedanken, Aharon
Liu, Xiaohui
Lin, Xiukun
Zinc-Doped Copper Oxide Nanocomposites Inhibit the Growth of Pancreatic Cancer by Inducing Autophagy Through AMPK/mTOR Pathway
title Zinc-Doped Copper Oxide Nanocomposites Inhibit the Growth of Pancreatic Cancer by Inducing Autophagy Through AMPK/mTOR Pathway
title_full Zinc-Doped Copper Oxide Nanocomposites Inhibit the Growth of Pancreatic Cancer by Inducing Autophagy Through AMPK/mTOR Pathway
title_fullStr Zinc-Doped Copper Oxide Nanocomposites Inhibit the Growth of Pancreatic Cancer by Inducing Autophagy Through AMPK/mTOR Pathway
title_full_unstemmed Zinc-Doped Copper Oxide Nanocomposites Inhibit the Growth of Pancreatic Cancer by Inducing Autophagy Through AMPK/mTOR Pathway
title_short Zinc-Doped Copper Oxide Nanocomposites Inhibit the Growth of Pancreatic Cancer by Inducing Autophagy Through AMPK/mTOR Pathway
title_sort zinc-doped copper oxide nanocomposites inhibit the growth of pancreatic cancer by inducing autophagy through ampk/mtor pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454023/
https://www.ncbi.nlm.nih.gov/pubmed/31001120
http://dx.doi.org/10.3389/fphar.2019.00319
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